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research-article2015
TAU0010.1177/1756287215585273Therapeutic Advances in UrologyML Blute, Jr., A Drewry
Therapeutic Advances in Urology
Review
Percutaneous biopsy for risk stratification of renal masses Michael L. Blute, Jr, Anna Drewry and Edwin Jason Abel
Ther Adv Urol 2015, Vol. 7(5) 265–274 DOI: 10.1177/ 1756287215585273 © The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Abstract: The increased use of abdominal imaging has led to identification of more patients with incidental renal masses, and renal mass biopsy (RMB) has become a popular method to evaluate unknown renal masses prior to definitive treatment. Pathologic data obtained from biopsy may be used to guide decisions for treatment and may include the presence or absence of malignant tumor, renal cell cancer subtype, tumor grade and the presence of other aggressive pathologic features. However, prior to using RMB for risk stratification, it is important to understand whether RMB findings are equivalent to pathologic analysis of surgical specimens and to identify any potential limitations of this approach. This review outlines the advantages and limitations of the current studies that evaluate RMB as a guide for treatment decision in patients with unknown renal masses. In multiple series, RMB has demonstrated low morbidity and a theoretical reduction in cost, if patients with benign tumors are identified from biopsy and can avoid subsequent treatment. However, when considering the routine use of RMB for risk stratification, it is important to note that biopsy may underestimate risk in some patients by undergrading, understaging or failing to identify aggressive tumor features. Future studies should focus on developing treatment algorithms that integrate RMB to identify the optimal use in risk stratification of patients with unknown renal masses.
Keywords: renal cell carcinoma, renal mass biopsy, risk stratification, small renal mass
Introduction The incidence and detection of renal cell carcinoma (RCC) has increased significantly over the past 50 years [Pantuck et al. 2001]. Improvements in cross-sectional imaging techniques have facilitated detection of asymptomatic small renal masses (SRMs) while causing a stage migration in RCC [Hollingsworth et al. 2006] with masses up to 4 cm constituting 48–66% of new diagnoses [Nguyen et al. 2006]. The etiology of unknown renal masses falls into three categories: aggressive cancers, slow-growing cancers and benign tumors [Frank et al. 2003] and treatment of renal tumors may include surgery, ablation or active surveillance. However, deciding among treatments is not always straightforward, especially for patients with major comorbidities or advanced age [Patel et al. 2012]. Many small RCCs are indolent with less than 5% of patients with nonmetastatic SRMs progressing to metastatic RCCs (mRCCs) within the first 5 years after treatment [Abel et al. 2010b;
Umbreit et al. 2012]. However, while the probability of developing mRCC is small, the consequences are significant because the prognosis for patients with RCC with metastases is dismal despite treatment with newer systemic agents [Heng et al. 2009]. Therefore, identifying aggressive tumors is critical to proper treatment, while the identification of more indolent tumors is also useful for selecting patients who may benefit from alternative approaches to treatment such as surveillance regimens.
Correspondence to: Edwin Jason Abel, MD Assistant Professor, Department of Urology, University of Wisconsin School of Medicine and Public Health, 1685 Highland Avenue, Madison, WI 53705-2281, USA [email protected] Michael L. Blute, Jr, MD Anna Drewry, BS Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
Renal mass biopsy (RMB) has become a popular diagnostic tool to evaluate renal masses and may provide important information prior to treatment [Volpe et al. 2007]. However, RMB should be compared with the gold standard for risk assessment in patients with nonmetastatic disease, which is based on pathologic evaluation of renal tumor specimens after surgery. Multiple pathologic predictors for metastatic recurrence and
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Therapeutic Advances in Urology 7(5) Table 1. Advantages and disadvantages of performing renal mass biopsy (RMB). Advantages of RMB
Disadvantages of RMB
By avoiding treatment in patients with benign tumors: Improved overall renal function Decreased treatment-related morbidity Decreased cost of treatment Improves informed consent for patients considering treatment Allows pathologic diagnosis for patients treated with ablation or surveillance
Complications related to biopsy procedure
cancer-specific survival have been described and validated, including nuclear grade, T stage and the presence of poor prognostic features such as sarcomatoid differentiation [Zisman et al. 2002; Sorbellini et al. 2005; Thompson et al. 2007; Abel et al. 2010b]. While percutaneous biopsy and three-dimensional imaging provide predictive data, it is unclear if information gained prior to surgery is equivalent to the pathologic assessment after surgery. The purpose of this review is to outline the data supporting and limiting the use of RMB for risk stratification in patients with renal masses. Rationale for renal mass biopsy Historically, patients diagnosed with renal masses would be treated with surgery and pathologic diagnosis would be made afterward from nephrectomy specimens. The rationale for surgery was the presumptive diagnosis of RCC since it is found in the majority of patients with incidental renal masses in surgical series [Frank et al. 2003]. However, the increased use of imaging has led to more frequent diagnosis of small incidental renal masses in patients who are often being treated for other cancers or serious medical comorbidities [Umbreit et al. 2012]. Deciding the best treatment for patients with renal masses can be especially difficult when considering possible competing causes of mortality for many patients [Kutikov et al. 2010]. In addition, alternatives to surgery such as thermal ablation [Choueiri et al. 2011] and active surveillance protocols [Smaldone et al. 2013] have been developed and may be more appropriate treatments for patients with serious comorbidities. As a result, RMB has become popular method for identifying renal malignancies prior to treatment [Leppert et al. 2014]. The optimal use of RMB for patients with incidental renal masses is debated and the proper role of biopsy for the evaluation of patients with
Additional cost of procedure Theoretical risk of tumor spreading
typical renal mass remains unclear. Although there are theoretical advantages and disadvantages with the use of RMB (Table 1), the choice to obtain a biopsy should be made individually based on the perceived risks and benefits for each patient. Similar to any diagnostic test, a thorough understanding of the ability and limitations of RMB is essential for physicians treating patients with renal masses. Risk stratification for treatment planning should be comprehensive considering patient comorbidities, data from RMB and imaging, as well the potential for inaccuracy when using these techniques. Depending on the institutional practice, pathological information reported from biopsy specimens may include the presence of neoplasm, tumor grade, histologic subtype, and the presence of aggressive features, for example, sarcomatoid or rhabdoid features. The ability of RMB to accurately diagnose these features will be examined individually. Renal mass biopsy: safety and cost It is appropriate to first consider the safety and cost of RMB prior to assessing its clinical utility. Potential complications of RMB include retroperitoneal hemorrhage, vascular complications, pneumothorax or biopsy tract seeding. However, the overall rates of post biopsy complications are low [Lane et al. 2008; Volpe et al. 2012] and complications requiring intervention are seen in less than 1% of patients from large modern series [Prince et al. 2014]. The most common complication following biopsy is bleeding from nearby vascular structures, the kidney parenchyma or the tumor itself. As biopsy techniques have evolved, the risk of significant hemorrhage has decreased [Caoili et al. 2002; Rybicki et al. 2003]. Similarly, the development of arteriovenous fistula or pneumothorax occurs in less than 1% of patients following biopsy [Leveridge et al. 2011]. One exceptionally rare complication which receives disproportionate attention is the possibility of
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ML Blute, Jr., A Drewry et al. biopsy tumor tract seeding. This complication has been reported in the literature twice in the last 20 years [Leveridge et al. 2011; Mullins and Rodriguez, 2013], despite a significant increase in the utilization of RMB over the same time period [Leppert et al. 2014]. Another concern when integrating biopsy into patient management of renal masses is the additional cost of undergoing a biopsy when surgery achieves both diagnosis and treatment objectives. However, if patients with benign tumors are spared the cost of treatment, biopsy may be cost effective. To address the cost effectiveness of RMB, Pandharipande and colleagues used a decisionanalytic Markhov model to compare cost effectiveness of using RMB to triage patient management to surveillance or empiric surgery for SRMs [Pandharipande et al. 2010]. They found that a biopsy strategy yielded a minimally improved quality-adjusted life expectancy of 4 days compared with surgery at a lower lifetime cost of $3466. In similar fashion, while again using a Markhov model, a more recent report compared immediate surgery with biopsy or surveillance in a hypothetical 60-year-old man with a SRM. When adjusting for quality of life, biopsy outperformed immediate surgery as a more cost-effective diagnostic strategy at $33,840 per quality-adjusted life year gained [Heilbrun et al. 2012]. Although biopsy did not yield the best survival, this study highlights that low-risk patients may be treated with surveillance for a T1a renal mass while benefiting from a cost-effective strategy. Ability of renal mass biopsy to diagnose the presence of malignancy The accuracy of RMB to diagnose malignancy depends on multiple factors, including the ability to target small tumors using imaging guidance, the ability to diagnose malignancy from small pathologic specimens, and the inherent sampling error when evaluating heterogeneous tumors. Although no prospective studies have evaluated fine needle aspiration (FNA) versus core biopsy techniques for accuracy, it should be noted that diagnoses from FNA sampling are considerably dependent on the experience of the cytopathologist, who may be present at the biopsy to confirm the adequacy of sampling [Volpe et al. 2007]. Nondiagnostic findings from RMB are present in 15–22% of large contemporary series [Shannon et al. 2008; Leveridge et al. 2011; Prince et al. 2014] (Table 2). Some of the variation in
incidence among series stems from the lack of a standardized definition for nondiagnostic RMB. Many series report only fibrosis or necrosis as nondiagnostic findings while other series include RMB with benign renal parenchyma when the tumor was ‘missed’. Nondiagnostic findings appear to be more common in patients with smaller tumors [Wang et al. 2009; Leveridge et al. 2011; Prince et al. 2014] and cystic features [Leveridge et al. 2011; Prince et al. 2014]. In addition, a longer distance from the skin to the tumor and a lack of enhancement with contrast imaging may also be associated with higher nondiagnostic rates [Prince et al. 2014]. Patient and tumor characteristics should be considered when deciding to obtain RMB, and lower overall nondiagnostic rates may be possible when selecting only patients with larger solid enhancing masses and shorter skin to tumor distance. When RMB is not diagnostic for either infection or a neoplasm, physicians should still suspect the presence of malignancy and consider repeating biopsy or proceeding with surgery or observation as indicated. However, there is minimal impact on risk stratification when physicians understand the continued risk of malignancy in patients with incidental renal masses and nondiagnostic RMB. Ability of renal mass biopsy to diagnose renal cell cancer subtypes Prior studies evaluating the concordance between biopsy specimens and surgical pathology for RCC subtype have ranged between 86% and 100% (Table 3) [Shannon et al. 2008; Wang et al. 2009; Millet et al. 2012]. High levels of concordance between biopsy and surgical pathology are especially noted in clear cell or conventional RCC [Shannon et al. 2008], which is the most common subtype of RCC [Lane et al. 2008]. Recent studies of non-clear cell RCC subtypes have also demonstrated high rates of concordance [Millet et al. 2012], with immunohistochemical staining facilitating diagnosis in some patients [Lane et al. 2008]. One important diagnostic consideration is the ability to differentiate between chromophobe RCC and oncocytoma, which may be achieved using a panel of tissue markers [Huang et al. 2009]. Historically, there was significant concern over the ability to distinguish oncocytoma from RCC both histologically and radiographically [Gakis et al. 2011] and surgical resection remained the only modality to diagnose and treat oncocytoma.
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Therapeutic Advances in Urology 7(5) Table 2. Renal mass biopsy series and nondiagnostic rate. Study
Biopsies
Nondiagnostic biopsy rate
Nondiagnostic definition
Maturen et al. [2007] Volpe et al. [2008] Prince et al. [2014] Leveridge et al. [2011] Lebret et al. [2007] Shannon et al. [2008] Vasudevan et al. [2006] Wang et al. [2009]
152 100
6 (3.9%) 16 (16%)
565
83 (14.7%)
345
67 (19.4%)
119
25 (21%)
235
51 (21.7%)
100 110
30 (30%) 10 (9%)
Insufficient tissue Insufficient tissue 1 RCC of 2 repeat biopsies Necrosis/fibrosis Insufficient tissue Nonrenal tissue Insufficient tissue 12 repeat biopsies revealed 8 RCCs Necrosis Inflammation 13 repeat biopsies revealed 11 RCCs Inflammation/necrosis Connective tissue Fat tissue Insufficient tissue 2 nondiagnostic biopsies were renal cell cancer after nephrectomy
Table 3. Studies comparing renal mass biopsy to surgical pathology. Study
Biopsy (n)
Subtype cancer diagnosis (%)
Grade concordance (%)
Grade concordance (%) (high or low)
Maturen et al. [2007] Volpe et al. [2008] Schmidbauer et al. [2008] Leveridge et al. [2011] Lebret et al. [2007] Blumenfeld et al. [2010] Millet et al. [2012]
59 100 60 100 52 67 61
98 66 96 88 86 82 100
70 68 76 64 46 43 75
Not shown 75 Not shown Not shown 74 64 93
Concern for hybrid tumors consisting of oncocytoma juxtaposed with malignant tissue [Waldert et al. 2010] caused many surgeons to recommend treatment for all patients despite a biopsy diagnosis of oncocytoma. However, recent series have suggested that hybrid tumors are exceptionally rare. Ginzburg and colleagues identified 147 solitary sporadic tumors that contained any element of oncocytoma or angiomyolipoma following nephrectomy [Ginzburg et al. 2014] and found less than 3% of tumors included coexistent malignant tissue, with no tumors having any high-grade components. Importantly, at a median follow up of 44 months, no patient with a hybrid tumor experienced local, regional or metastatic progression. These results are encouraging and support less aggressive approaches for renal oncocytoma management.
Ability of renal mass biopsy to evaluate tumor grade in renal cell carcinoma Tumor grade is often a reliable determinant of tumor behavior [Ficarra et al. 2010]. However, with recent studies demonstrating considerable tumor heterogeneity within RCC tumors, biopsy grade may be less accurate due to sampling error [Gerlinger et al. 2012]. To evaluate the possibility that tumor heterogeneity can lead to misrepresentation of biopsy grade, Ball and colleagues reevaluated 32 pT1a RCC surgical specimens for grade heterogeneity. Specimens consisted of either clear cell or papillary RCC with high- and low-grade features. The authors showed that 26 samples (81.3%) were heterogeneous and 15 of 16 high-grade tumors also exhibited significant low-grade components [Ball et al. 2015]. With significant grade heterogeneity demonstrated among high-grade
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ML Blute, Jr., A Drewry et al. cancers, it is obvious how biopsy sampling may miss a component of high-grade disease and underestimate RCC risk. Previous series substantiate the inaccuracy of predicting tumor grade from biopsy specimens [Neuzillet et al. 2004; Lebret et al. 2007; Millet et al. 2012], which has implications for reporting and interpreting RMB results. A recent report identified grade heterogeneity in single tumors in up to 25% of cases [Halverson et al. 2013]. Undergrading biopsy specimens could be significant clinically for some patients if they choose to defer treatment based on risk assessment from an erroneous tumor grade. The accuracy of tumor grading on RMB specimens varies considerably among series (43–75%) [Tomaszewski et al. 2014], and no studies included more than 100 patients. Although high-grade tumors are rare in small localized tumors [Abel et al. 2010b], the limited ability to predict tumor grade must be considered when making treatment decisions. Ability of preoperative imaging to evaluate tumor stage in small renal cell carcinoma Radiologic imaging may be used to evaluate the clinical T stage of the primary tumor, which is an important predictor of RCC recurrence and survival [Zisman et al. 2002; Sorbellini et al. 2005; Thompson et al. 2007], although clinical staging is not equivalent to pathologic staging in RCC. Renal masses equal to or less than 7 cm are staged as T1 or T3a when tumors invade into perinephric fat. However, imaging does not reliably identify perinephric fat invasion [Hedgire et al. 2013], which is an important predictor of poor outcomes in RCC. In a recent study of 860 patients with RCC stage T1–3 [Yoo et al. 2008], the authors showed a significant difference in disease-free survival [hazard ratio 2.21, 95% confidence interval (CI) 1.01–4.84; p = 0.05] among patients with fat invasion compared with lower stage disease. Furthermore, 85% of patients with recurrence of T3a tumors greater than 7 cm died of RCC compared with 33% of patients who had recurrence with tumors less than 7 cm (p = 0.001). When evaluating patients with tumors less than 7 cm specifically, metastatic recurrence was 14.6% compared with 6.0% in patients with fat invasion and without fat invasion, respectively [Ginzburg et al. 2014]. Siddiqui and colleagues also evaluated the significance of T3a disease across a spectrum of tumor size and found risk ratios of death for RCC fat invasion to be 6.15 (1.84–20.50, p = 0.003), 4.12 (2.50–6.78, p < 0.001) and 2.13 (1.53–2.97, p < 0.001) for tumors 4 cm or smaller, 4–7 cm, and more than 7
cm, respectively [Siddiqui et al. 2007]. The association of death with fat invasion remained significant on multivariate analysis. Attempts to identify T3a tumors based on preoperative imaging have demonstrated poor accuracy [Sokhi et al. 2015]. A recent study compared a combined approach of computed tomography/magnetic resonance imaging with nephrectomy assessment for perinephric fat invasion in renal masses with median diameter of 4.5 cm. Of 55 patients who were diagnosed with fat invasion, 26 (47.2%) did not have pathological fat invasion [Huang et al. 2009]. Likewise, detection of renal sinus fat invasion may carry equal importance as these tumors have been shown to be more aggressive than tumors with perinephric fat involvement [Thompson et al. 2005]. Unless more reliable methods for detecting perinephric fat and renal sinus fat invasion [Kim et al. 2014] are developed, understaging will likely remain a persistent limitation for approximately 5–10% of patients with clinically localized tumors that are pathologically T3a [Siddiqui et al. 2007; Gorin et al. 2013]. Ability of biopsy to identify aggressive pathologic features in small renal masses Sarcomatoid dedifferentiation is an aggressive pathologic feature that may be present with any RCC subtype [Lane et al. 2008] and is associated with poor outcomes [Zhang et al. 2014]. However, the ability of percutaneous biopsy to identify sarcomatoid features may be limited by sampling error. In patients with mRCC, sarcomatoid dedifferentiation was identified preoperatively in only 11.8% and 9.2% of primary tumors and metastatic tumors, respectively [Chao et al. 2001; Crispen et al. 2011]. As seen with high tumor grade [Ball et al. 2015], sarcomatoid dedifferentiation may only be present in a minority of tissue and percutaneous biopsy is therefore prone to sampling error. However, sarcomatoid pathology is rare in lower stage tumors, with one study of 925 patients with pT1 and pT2 tumors demonstrating less than 1% incidence of sarcomatoid features in the surgical specimens [Abel et al. 2010b]. Given the rarity in low-stage tumors, the inability to identify sarcomatoid features from biopsy is likely less significant for this population. Should the limitations of biopsy limit its use for risk stratification of incidental renal masses? There are notable limitations (Table 4) when using RMB that may result in underestimation of risk in patients with nonmetastatic disease and incidental renal masses. These limitations should
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Therapeutic Advances in Urology 7(5) Table 4. Potential limitations when using renal mass biopsy for estimating risk from incidental renal masses. Nondiagnostic findings in approximately 15% of patients Underestimation of grade in approximately 25% of patients Underestimation of stage in approximately 5–10% of patients Failure to identify aggressive pathology, that is sarcomatoid or rhabdoid features
be considered when ordering RMB for healthy patients considering surgical treatment, because of the risk of mRCC. However, the potential benefits of RMB for many patients should not be dismissed regardless of RMB limitations. Biopsy is safe and likely cost efficient when used judiciously and has demonstrated the ability to reliably identify malignant and benign tumors in patients with incidental renal masses. For many patients with incidental renal masses, RMB can provide information that is helpful for management. Patient selection for renal mass biopsy Selecting appropriate patients for RMB is important to improve the evaluation of incidental renal masses and maximize the percentage of patients who benefit from this procedure. Patients who are considering active surveillance or thermal ablation should receive RMB in order to plan appropriate follow-up protocols [Volpe et al. 2012]. When benign masses are identified, patients may receive minimal follow up as appropriate. Similarly, in patients who are borderline candidates for surgery, the identification of benign masses allows surgery to be deferred. However, in patients with comorbidities that significantly limit a patient’s life expectancy, RMB should only be ordered when the information gained from RMB may change the patient’s further treatment. Patients with atypical renal masses that are concerning for infection or metastatic lesions are ideal patients for RMB. In addition, very young patients or those with masses that are suspicious for nonRCC lesions may benefit from identification of malignancy, as treatment for some tumors such as renal lymphomas [Cyriac et al. 2010] or sarcomas [De Visschere et al. 2013] may involve upfront chemotherapy or radiation therapy. Deciding which patients should receive RMB among patients who are otherwise acceptable surgical candidates is less clear. However, RMB does improve informed consent for patients who are considering surgical treatment for their renal masses. When patients are given the diagnosis of cancer from RMB, they may be more willing to be treated with surgical therapy.
Conversely, patients with benign masses identified from RMB may be more willing to undergo observation. Patients who are suspected of having metastatic renal masses may also obtain RMB for diagnosis, especially as the majority of patients with mRCC are not treated with cytoreductive nephrectomy [Tsao et al. 2012; Minnillo et al. 2014], but need a pathologic diagnosis prior to treatment. Despite the development of multiple new therapies, patients with mRCC continue to have a poor prognosis [Heng et al. 2009]. Aggressive features such as sarcomatoid dedifferentiation are associated with short overall survival and may not benefit from cytoreductive surgery [Mian et al. 2002; Molina et al. 2011; Przybycin et al. 2014]. An analysis of 417 patients undergoing cytoreductive nephrectomy for mRCC compared those with sarcomatoid histology with conventional RCC [Shuch et al. 2009]. Median survival in patients with sarcomatoid features was just 4.9 months compared with 17.7 months for conventional clear cell RCC (p < 0.001). However, sarcomatoid features are difficult to identify because of sampling error in large tumors or metastases using standard biopsy techniques [Abel et al. 2010a, 2012]. Similarly, distinguishing non-clear cell tumor subtypes may be helpful as targeted therapy appear to be less effective [Vera-Badillo et al. 2014]. In a meta-analysis consisting of 49 studies and 7771 patients treated with targeted therapy for mRCC, the median progression-free survival and overall survival for nonclear cell RCC was 7.4 and 13.4 months, respectively, compared with 10.5 and 15.7 months for clear cell RCC, respectively (p < 0.001). While cytoreductive nephrectomy may provide a survival benefit in metastatic non-clear cell RCC [Aizer et al. 2014], preoperative identification of non-clear cell RCC from RMB may allow enrollment in clinical trials of presurgical therapy. Clinical protocols for decision making using renal mass biopsy for incidental renal masses Information gained from biopsy may allow improved patient selection for surgery and other
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ML Blute, Jr., A Drewry et al. treatments. Several studies have critically analyzed the ability of RMB to impact decision making, although the optimal use remains debated. Halverson and colleagues evaluated 133 patients with SRMs and assigned patients to surgery or surveillance based on RMB findings [Halverson et al. 2013]. Of the 97 tumors that were assigned to surgery, agreement between biopsy and final pathology was 100% for identifying malignancy and 94% for distinguishing histology. According to their model, biopsy correctly assigned all 97 patients (90% sensitivity) to surgery while 11 of 36 patients were incorrectly assigned to surveillance based on final pathology. For the entire cohort, agreement between biopsy and final pathology was 92% (95% CI 0.64–0.90). Similarly, Tan et al. analyzed the role of RMB for SRMs to guide decision making [Tan et al. 2012]. The authors determined indications for RMB in 78 (38%) of 204 patients with T1 tumors and identified body mass index greater than 25, juxtahilar tumor location, and high R.E.N.A.L. (it is an acronym for Radius, Exophytic/endophytic properties, Nearness of tumor to hilum, Anterio/posterior, Location) nephrometry score as factors associated with use of RMB on multivariate analysis. The authors conclude that RMB was able to direct treatmentrelated decision making, with surveillance planned more often for patients with favorable and benign histology and surgical management reserved for aggressive tumors (p < 0.001). The approaches in these two studies highlight the potential for RMB to improve clinical decision making as more asymptomatic renal tumors are diagnosed by cross-sectional imaging. However, the limitations of RMB (Table 4) should be discussed with patients who are risk stratified using these approaches, given the risks with this approach. Biopsy for evaluation of incidental renal masses: potential impact on patient care Approximately 20–30% of renal masses are benign following surgical resection [Frank et al. 2003; Gill et al. 2003]. If RMB could reliably identify these patients prior to surgery, a significant proportion of patients with benign tumors could be spared surgery. Despite noted RMB limitations (Table 4), the majority of series have demonstrated accuracy to distinguish between benign and malignant tumors, when biopsy findings are diagnostic. Avoiding treatment in patients with benign tumors would improve overall renal function, as fewer patients would have treatmentrelated loss of renal function. In addition, patients
with benign tumors could be spared the risk of treatment-related complications and the cost of treatment. Another potential impact of routine RMB that is difficult to measure empirically is the improved ability for informed consent after RMB in patients considering definitive management. Patient awareness of biopsy-proven malignancy may lead to a more informed and assertive decision for management, which appears reasonable given the low procedural morbidity. When atypical renal masses are diagnosed from imaging [Leveridge et al. 2010], RMB also allows for distinguishing between rare tumors and uncommon presentations of common tumors, which may also impact management for tumors when nonsurgical treatment is indicated. Conclusion Risk stratifying patients with unknown renal masses is important when choosing an acceptable treatment. RMB is associated with a low incidence of complications and may provide valuable information to help patients and physicians decide among treatments. It is important to recognize that RMB may underestimate risk and has limited accuracy when evaluating tumor grade, aggressive pathologic features or T stage. Future studies are necessary to evaluate the optimal use of biopsy in the evaluation and management of incidental renal masses. Funding No outside funding was used in this project. Conflict of interest statement The authors declare that there is no conflict of interest.
References Abel, E., Carrasco, A., Culp, S., Matin, S., Tamboli, P., Tannir, N. et al. (2012) Limitations of preoperative biopsy in patients with metastatic renal cell carcinoma: comparison to surgical pathology in 405 cases. BJU Int 110: 1742–1746. Abel, E., Culp, S., Matin, S., Tamboli, P., Wallace, M., Jonasch, E. et al. (2010a) Percutaneous biopsy of primary tumor in metastatic renal cell carcinoma to predict high risk pathological features: comparison with nephrectomy assessment. J Urol 184: 1877–1881. Abel, E., Culp, S., Meissner, M., Matin, S., Tamboli, P. and Wood, C. (2010b) Identifying the risk of
http://tau.sagepub.com 271
Therapeutic Advances in Urology 7(5) disease progression after surgery for localized renal cell carcinoma. BJU Int 106: 1277–1283. Aizer, A., Urun, Y., McKay, R., Kibel, A., Nguyen, P. and Choueiri, T. (2014) Cytoreductive nephrectomy in patients with metastatic non-clear-cell renal cell carcinoma (RCC). BJU Int 113: E67–E74. Ball, M., Bezerra, S., Gorin, M., Cowan, M., Pavlovich, C., Pierorazio, P. et al. (2015) Grade heterogeneity in small renal masses: potential implications for renal mass biopsy. J Urol 193: 36–40. Blumenfeld, A.J., Guru, K., Fuchs, G.J. and Kim, H.L. (2010) Percutaneous biopsy of renal cell carcinoma underestimates nuclear grade. Urology 76(3): 610–603. Caoili, E., Bude, R., Higgins, E., Hoff, D. and Nghiem, H. (2002) Evaluation of sonographically guided percutaneous core biopsy of renal masses. AJR Am J Roentgenol 179: 373–378. Chao, D., Zisman, A., Freedland, S., Pantuck, A., Said, J. and Belldegrun, A. (2001) Sarcomatoid renal cell carcinoma: basic biology, clinical behavior and response to therapy. Urol Oncol 6: 231–238. Choueiri, T., Schutz, F., Hevelone, N., Nguyen, P., Lipsitz, S., Williams, S. et al. (2011) Thermal ablation vs surgery for localized kidney cancer: a Surveillance, Epidemiology, and End Results (SEER) database analysis. Urology 78: 93–98. Crispen, P., Breau, R., Allmer, C., Lohse, C., Cheville, J., Leibovich, B. et al. (2011) Lymph node dissection at the time of radical nephrectomy for highrisk clear cell renal cell carcinoma: indications and recommendations for surgical templates. Eur Urol 59: 18–23. Cyriac, S., Rejiv, R., Shirley, S. and Sagar, G. (2010) Primary renal lymphoma mimicking renal cell carcinoma. Indian J Urol 26: 441–443. De Visschere, P., De Potter, A., Claus, F., Mulkens, T., Oyen, R., Verbaeys, A. et al. (2013) PNET/ Ewing’s sarcoma of the kidney: imaging findings in two cases. JBR-BTR 96: 75–77. Ficarra, V., Brunelli, M., Cheng, L., Kirkali, Z., Lopez-Beltran, A., Martignoni, G. et al. (2010) Prognostic and therapeutic impact of the histopathologic definition of parenchymal epithelial renal tumors. Eur Urol 58: 655–668.
Gerlinger, M., Rowan, A., Horswell, S., Larkin, J., Endesfelder, D., Gronroos, E. et al. (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366: 883–892. Gill, I., Matin, S., Desai, M., Kaouk, J., Steinberg, A., Mascha, E. et al. (2003) Comparative analysis of laparoscopic versus open partial nephrectomy for renal tumors in 200 patients. J Urol 170: 64–68. Ginzburg, S., Uzzo, R., Al-Saleem, T., Dulaimi, E., Walton, J., Corcoran, A. et al. (2014) Coexisting hybrid malignancy in a solitary sporadic solid benign renal mass: implications for treating patients following renal biopsy. J Urol 191: 296–300. Gorin, M., Ball, M., Pierorazio, P., Tanagho, Y., Bhayani, S., Kaouk, J. et al. (2013) Outcomes and predictors of clinical T1 to pathological T3a tumor up-staging after robotic partial nephrectomy: a multiinstitutional analysis. J Urol 190: 1907–1911. Halverson, S., Kunju, L., Bhalla, R., Gadzinski, A., Alderman, M., Miller, D. et al. (2013) Accuracy of determining small renal mass management with risk stratified biopsies: confirmation by final pathology. J Urol 189: 441–446. Hedgire, S., Elmi, A., Nadkarni, N., Cao, K., McDermott, S. and Harisinghani, M. (2013) Preoperative evaluation of perinephric fat invasion in patients with renal cell carcinoma: correlation with pathological findings. Clin Imaging 37: 91–96. Heilbrun, M., Yu, J., Smith, K., Dechet, C., Zagoria, R. and Roberts, M. (2012) The cost-effectiveness of immediate treatment, percutaneous biopsy and active surveillance for the diagnosis of the small solid renal mass: evidence from a Markov model. J Urol 187: 39–43. Heng, D., Xie, W., Regan, M., Warren, M., Golshayan, A., Sahi, C. et al. (2009) Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 27: 5794–5799. Hollingsworth, J., Miller, D., Daignault, S. and Hollenbeck, B. (2006) Rising incidence of small renal masses: a need to reassess treatment effect. J Natl Cancer Inst 98: 1331–1334.
Frank, I., Blute, M., Cheville, J., Lohse, C., Weaver, A. and Zincke, H. (2003) Solid renal tumors: an analysis of pathological features related to tumor size. J Urol 170: 2217–2220.
Huang, W., Kanehira, K., Drew, S. and Pier, T. (2009) Oncocytoma can be differentiated from its renal cell carcinoma mimics by a panel of markers an automated tissue microarray study. Appl Immunohistochem Mol Morphol 17: 12–17.
Gakis, G., Kramer, U., Schilling, D., Kruck, S., Stenzl, A. and Schlemmer, H. (2011) Small renal oncocytomas: differentiation with multiphase CT. Eur J Radiol 80: 274–278.
Kim, C., Choi, H. and Cho, K. (2014) Diagnostic value of multidetector computed tomography for renal sinus fat invasion in renal cell carcinoma patients. Eur J Radiol 83: 914–918.
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ML Blute, Jr., A Drewry et al. Kutikov, A., Egleston, B., Wong, Y. and Uzzo, R. (2010) Evaluating overall survival and competing risks of death in patients with localized renal cell carcinoma using a comprehensive nomogram. J Clin Oncol 28: 311–317. Lane, B., Samplaski, M., Herts, B., Zhou, M., Novick, A. and Campbell, S. (2008) Renal mass biopsy–a renaissance? J Urol 179: 20–27. Lebret, T., Poulain, J., Molinie, V., Herve, J., Denoux, Y., Guth, A. et al. (2007) Percutaneous core biopsy for renal masses: indications, accuracy and results. J Urol 178: 1184–1188; discussion 1188. Leppert, J., Hanley, J., Wagner, T., Chung, B., Srinivas, S., Chertow, G. et al. (2014) Utilization of renal mass biopsy in patients with renal cell carcinoma. Urology 83: 774–779. Leveridge, M., Bostrom, P., Koulouris, G., Finelli, A. and Lawrentschuk, N. (2010) Imaging renal cell carcinoma with ultrasonography, CT and MRI. Nat Rev Urol 7: 311–325. Leveridge, M., Finelli, A., Kachura, J., Evans, A., Chung, H., Shiff, D. et al. (2011) Outcomes of small renal mass needle core biopsy, nondiagnostic percutaneous biopsy, and the role of repeat biopsy. Eur Urol 60: 578–584. Maturen, K.E., Nghiem, H.V., Caoili, E.M., Higgins, E.G., Wolf, J.S. Jr. and Wood, D.P. Jr. (2007) Renal mass core biopsy: accuracy and impact on clinical management. AJR Am J Roentgenol 188(2): 563–570. Mian, B., Bhadkamkar, N., Slaton, J., Pisters, P., Daliani, D., Swanson, D. et al. (2002) Prognostic factors and survival of patients with sarcomatoid renal cell carcinoma. J Urol 167: 65–70. Millet, I., Curros, F., Serre, I., Taourel, P. and Thuret, R. (2012) Can renal biopsy accurately predict histological subtype and Fuhrman grade of renal cell carcinoma? J Urol 188: 1690–1694. Minnillo, B., Zhu, H., Maurice, M. and Abouassaly, R. (2014) Trends in cytoreductive nephrectomy in the eras of immuno and targeted therapy. J Clin Oncol 32(Suppl. 4): abstract 472. Molina, A., Tickoo, S., Ishill, N., Trinos, M., Schwartz, L., Patil, S. et al. (2011) Sarcomatoidvariant renal cell carcinoma: treatment outcome and survival in advanced disease. Am J Clin Oncol 34: 454–459. Mullins, J. and Rodriguez, R. (2013) Renal cell carcinoma seeding of a percutaneous biopsy tract. Can Urol Assoc J 7: E176–E179. Neuzillet, Y., Lechevallier, E., Andre, M., Daniel, L. and Coulange, C. (2004) Accuracy and clinical role of fine needle percutaneous biopsy with computerized
tomography guidance of small (less than 4.0 cm) renal masses. J Urol 171: 1802–1805. Nguyen, M., Gill, I. and Ellison, L. (2006) The evolving presentation of renal carcinoma in the United States: trends from the surveillance, epidemiology, and end results program. J Urol 176: 2397–2400. Pandharipande, P., Gervais, D., Hartman, R., Harisinghani, M., Feldman, A., Mueller, P. et al. (2010) Renal mass biopsy to guide treatment decisions for small incidental renal tumors: a costeffectiveness analysis. Radiology 256: 836–846. Pantuck, A., Zisman, A. and Belldegrun, A. (2001) The changing natural history of renal cell carcinoma. J Urol 166: 1611–1623. Patel, N., Cranston, D., Akhtar, M., George, C., Jones, A., Leiblich, A. et al. (2012) Active surveillance of small renal masses offers short-term oncological efficacy equivalent to radical and partial nephrectomy. BJU Int 110: 1270–1275. Prince, J., Bultman, E., Hinshaw, L., Drewry, A., Blute, M., Best, S. et al. (2014) Patient and tumor characteristics can predict non-diagnostic renal mass biopsy findings. J Urol 5347: 05062–05069. Przybycin, C., McKenney, J., Reynolds, J., Campbell, S., Zhou, M., Karafa, M. et al. (2014) Rhabdoid differentiation is associated with aggressive behavior in renal cell carcinoma: a clinicopathologic analysis of 76 cases with clinical follow-up. Am J Surg Pathol 38: 1260–1265. Rybicki, F., Shu, K., Cibas, E., Fielding, J., van Sonnenberg, E. and Silverman, S. (2003) Percutaneous biopsy of renal masses: sensitivity and negative predictive value stratified by clinical setting and size of masses. AJR Am J Roentgenol 180: 1281–1287. Schmidbauer, J., Remzi, M., Memarsadeghi, M., Haitel A., Klingler, H.C., Katzenbeisser, D. et al. (2008) Diagnostic accuracy of computed tomographyguided percutaneous biopsy of renal masses. Eur Urol 53(5): 1003–1011. Shannon, B., Cohen, R., de Bruto, H. and Davies, R. (2008) The value of preoperative needle core biopsy for diagnosing benign lesions among small, incidentally detected renal masses. J Urol 180: 1257–1261; discussion 1261. Shuch, B., Said, J., La Rochelle, J., Zhou, Y., Li, G., Klatte, T. et al. (2009) Cytoreductive nephrectomy for kidney cancer with sarcomatoid histology – is up-front resection indicated and, if not, is it avoidable? J Urol 182: 2164–2171. Siddiqui, S., Frank, I., Leibovich, B., Cheville, J., Lohse, C., Zincke, H. et al. (2007) Impact of tumor size on the predictive ability of the pT3a primary tumor classification for renal cell carcinoma. J Urol 177: 59–62.
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Therapeutic Advances in Urology 7(5) Smaldone, M., Corcoran, A. and Uzzo, R. (2013) Active surveillance of small renal masses. Nat Rev Urol 10: 266–274. Sokhi, H, Mok, W. and Patel, U. (2015) Stage T3a renal cell carcinoma: staging accuracy of CT for sinus fat, perinephric fat or renal vein invasion. Br J Radiol 88: 20140504. Sorbellini, M., Kattan, M., Snyder, M., Reuter, V., Motzer, R., Goetzl, M. et al. (2005) A postoperative prognostic nomogram predicting recurrence for patients with conventional clear cell renal cell carcinoma. J Urol 173: 48–51. Tan, H., Jacobs, B., Hafez, K., Montgomery, J., Weizer, A., Wood, D. et al. (2012) Understanding the role of percutaneous biopsy in the management of patients with a small renal mass. Urology 79: 372–377. Thompson, R., Leibovich, B., Cheville, J., Webster, W., Lohse, C., Kwon, E. et al. (2005) Is renal sinus fat invasion the same as perinephric fat invasion for pT3a renal cell carcinoma? J Urol 174: 1218–1221. Thompson, R., Leibovich, B., Lohse, C., Cheville, J., Zincke, H., Blute, M. et al. (2007) Dynamic outcome prediction in patients with clear cell renal cell carcinoma treated with radical nephrectomy: the D-SSIGN score. J Urol 177: 477–480.
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Vera-Badillo, F., Templeton, A., Duran, I., Ocana, A., de Gouveia, P., Aneja, P. et al. (2014) Systemic therapy for non-clear cell renal cell carcinomas: a systematic review and meta-analysis. Eur Urol 67: 740–749. Volpe, A., Finelli, A., Gill, I., Jewett, M., Martignoni, G., Polascik, T. et al. (2012) Rationale for percutaneous biopsy and histologic characterisation of renal tumours. Eur Urol 62: 491–504. Volpe, A., Kachura, J., Geddie, W., Evans, A., Gharajeh, A., Saravanan, A. et al. (2007) Techniques, safety and accuracy of sampling of renal tumors by fine needle aspiration and core biopsy. J Urol 178: 379–386. Volpe, A., Mattar, K., Finelli, A., Kachura, J.R., Evans, A.J., Geddie, W.R. et al. (2008) Contemporary results of percutaneous biopsy of 100 small renal masses: a single center experience. J Urol 180(6): 2333–2337. Waldert, M., Klatte, T., Haitel, A., Ozsoy, M., Schmidbauer, J., Marberger, M. et al. (2010) Hybrid renal cell carcinomas containing histopathologic features of chromophobe renal cell carcinomas and oncocytomas have excellent oncologic outcomes. Eur Urol 57: 661–665.
Tomaszewski, J., Uzzo, R. and Smaldone, M. (2014) Heterogeneity and renal mass biopsy: a review of its role and reliability. Cancer Biol Med 11: 162–172.
Wang, R., Wolf, J., Wood, D., Higgins, E. and Hafez, K. (2009) Accuracy of percutaneous core biopsy in management of small renal masses. Urology 73: 586–590; discussion 590–591.
Tsao, C., Small, A., Moshier, E., Gartrell, B., Wisnivesky, J., Sonpavde, G. et al. (2012) Trends in the use of cytoreductive nephrectomy in the United States. Clin Genitourin Cancer 10: 159–163.
Yoo, C., Song, C., Hong, J., Kim, C. and Ahn, H. (2008) Prognostic significance of perinephric fat infiltration and tumor size in renal cell carcinoma. J Urol 180: 486–491; discussion 491.
Umbreit, E., Shimko, M., Childs, M., Lohse, C., Cheville, J., Leibovich, B. et al. (2012) Metastatic potential of a renal mass according to original tumour size at presentation. BJU Int 109: 190–194; discussion 194.
Zhang, B., Thompson, R., Lohse, C., Leibovich, B., Boorjian, S., Cheville, J. et al. (2014) A novel prognostic model for patients with sarcomatoid renal cell carcinoma. BJU Int 115: 405–411.
Vasudevan, A., Davies, R.J., Shannon, B.A. and Cohen, R.J. (2006) Incidental renal tumours: the frequency of benign lesions and the role of preoperative core biopsy. BJU Int 97(5): 946–949.
Zisman, A., Pantuck, A., Wieder, J., Chao, D., Dorey, F., Said, J. et al. (2002) Risk group assessment and clinical outcome algorithm to predict the natural history of patients with surgically resected renal cell carcinoma. J Clin Oncol 20: 4559–4566.
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research-article2015
TAU0010.1177/1756287215585273Therapeutic Advances in UrologyML Blute, Jr., A Drewry
Therapeutic Advances in Urology
Review
Percutaneous biopsy for risk stratification of renal masses Michael L. Blute, Jr, Anna Drewry and Edwin Jason Abel
Ther Adv Urol 2015, Vol. 7(5) 265–274 DOI: 10.1177/ 1756287215585273 © The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Abstract: The increased use of abdominal imaging has led to identification of more patients with incidental renal masses, and renal mass biopsy (RMB) has become a popular method to evaluate unknown renal masses prior to definitive treatment. Pathologic data obtained from biopsy may be used to guide decisions for treatment and may include the presence or absence of malignant tumor, renal cell cancer subtype, tumor grade and the presence of other aggressive pathologic features. However, prior to using RMB for risk stratification, it is important to understand whether RMB findings are equivalent to pathologic analysis of surgical specimens and to identify any potential limitations of this approach. This review outlines the advantages and limitations of the current studies that evaluate RMB as a guide for treatment decision in patients with unknown renal masses. In multiple series, RMB has demonstrated low morbidity and a theoretical reduction in cost, if patients with benign tumors are identified from biopsy and can avoid subsequent treatment. However, when considering the routine use of RMB for risk stratification, it is important to note that biopsy may underestimate risk in some patients by undergrading, understaging or failing to identify aggressive tumor features. Future studies should focus on developing treatment algorithms that integrate RMB to identify the optimal use in risk stratification of patients with unknown renal masses.
Keywords: renal cell carcinoma, renal mass biopsy, risk stratification, small renal mass
Introduction The incidence and detection of renal cell carcinoma (RCC) has increased significantly over the past 50 years [Pantuck et al. 2001]. Improvements in cross-sectional imaging techniques have facilitated detection of asymptomatic small renal masses (SRMs) while causing a stage migration in RCC [Hollingsworth et al. 2006] with masses up to 4 cm constituting 48–66% of new diagnoses [Nguyen et al. 2006]. The etiology of unknown renal masses falls into three categories: aggressive cancers, slow-growing cancers and benign tumors [Frank et al. 2003] and treatment of renal tumors may include surgery, ablation or active surveillance. However, deciding among treatments is not always straightforward, especially for patients with major comorbidities or advanced age [Patel et al. 2012]. Many small RCCs are indolent with less than 5% of patients with nonmetastatic SRMs progressing to metastatic RCCs (mRCCs) within the first 5 years after treatment [Abel et al. 2010b;
Umbreit et al. 2012]. However, while the probability of developing mRCC is small, the consequences are significant because the prognosis for patients with RCC with metastases is dismal despite treatment with newer systemic agents [Heng et al. 2009]. Therefore, identifying aggressive tumors is critical to proper treatment, while the identification of more indolent tumors is also useful for selecting patients who may benefit from alternative approaches to treatment such as surveillance regimens.
Correspondence to: Edwin Jason Abel, MD Assistant Professor, Department of Urology, University of Wisconsin School of Medicine and Public Health, 1685 Highland Avenue, Madison, WI 53705-2281, USA [email protected] Michael L. Blute, Jr, MD Anna Drewry, BS Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
Renal mass biopsy (RMB) has become a popular diagnostic tool to evaluate renal masses and may provide important information prior to treatment [Volpe et al. 2007]. However, RMB should be compared with the gold standard for risk assessment in patients with nonmetastatic disease, which is based on pathologic evaluation of renal tumor specimens after surgery. Multiple pathologic predictors for metastatic recurrence and
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Therapeutic Advances in Urology 7(5) Table 1. Advantages and disadvantages of performing renal mass biopsy (RMB). Advantages of RMB
Disadvantages of RMB
By avoiding treatment in patients with benign tumors: Improved overall renal function Decreased treatment-related morbidity Decreased cost of treatment Improves informed consent for patients considering treatment Allows pathologic diagnosis for patients treated with ablation or surveillance
Complications related to biopsy procedure
cancer-specific survival have been described and validated, including nuclear grade, T stage and the presence of poor prognostic features such as sarcomatoid differentiation [Zisman et al. 2002; Sorbellini et al. 2005; Thompson et al. 2007; Abel et al. 2010b]. While percutaneous biopsy and three-dimensional imaging provide predictive data, it is unclear if information gained prior to surgery is equivalent to the pathologic assessment after surgery. The purpose of this review is to outline the data supporting and limiting the use of RMB for risk stratification in patients with renal masses. Rationale for renal mass biopsy Historically, patients diagnosed with renal masses would be treated with surgery and pathologic diagnosis would be made afterward from nephrectomy specimens. The rationale for surgery was the presumptive diagnosis of RCC since it is found in the majority of patients with incidental renal masses in surgical series [Frank et al. 2003]. However, the increased use of imaging has led to more frequent diagnosis of small incidental renal masses in patients who are often being treated for other cancers or serious medical comorbidities [Umbreit et al. 2012]. Deciding the best treatment for patients with renal masses can be especially difficult when considering possible competing causes of mortality for many patients [Kutikov et al. 2010]. In addition, alternatives to surgery such as thermal ablation [Choueiri et al. 2011] and active surveillance protocols [Smaldone et al. 2013] have been developed and may be more appropriate treatments for patients with serious comorbidities. As a result, RMB has become popular method for identifying renal malignancies prior to treatment [Leppert et al. 2014]. The optimal use of RMB for patients with incidental renal masses is debated and the proper role of biopsy for the evaluation of patients with
Additional cost of procedure Theoretical risk of tumor spreading
typical renal mass remains unclear. Although there are theoretical advantages and disadvantages with the use of RMB (Table 1), the choice to obtain a biopsy should be made individually based on the perceived risks and benefits for each patient. Similar to any diagnostic test, a thorough understanding of the ability and limitations of RMB is essential for physicians treating patients with renal masses. Risk stratification for treatment planning should be comprehensive considering patient comorbidities, data from RMB and imaging, as well the potential for inaccuracy when using these techniques. Depending on the institutional practice, pathological information reported from biopsy specimens may include the presence of neoplasm, tumor grade, histologic subtype, and the presence of aggressive features, for example, sarcomatoid or rhabdoid features. The ability of RMB to accurately diagnose these features will be examined individually. Renal mass biopsy: safety and cost It is appropriate to first consider the safety and cost of RMB prior to assessing its clinical utility. Potential complications of RMB include retroperitoneal hemorrhage, vascular complications, pneumothorax or biopsy tract seeding. However, the overall rates of post biopsy complications are low [Lane et al. 2008; Volpe et al. 2012] and complications requiring intervention are seen in less than 1% of patients from large modern series [Prince et al. 2014]. The most common complication following biopsy is bleeding from nearby vascular structures, the kidney parenchyma or the tumor itself. As biopsy techniques have evolved, the risk of significant hemorrhage has decreased [Caoili et al. 2002; Rybicki et al. 2003]. Similarly, the development of arteriovenous fistula or pneumothorax occurs in less than 1% of patients following biopsy [Leveridge et al. 2011]. One exceptionally rare complication which receives disproportionate attention is the possibility of
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ML Blute, Jr., A Drewry et al. biopsy tumor tract seeding. This complication has been reported in the literature twice in the last 20 years [Leveridge et al. 2011; Mullins and Rodriguez, 2013], despite a significant increase in the utilization of RMB over the same time period [Leppert et al. 2014]. Another concern when integrating biopsy into patient management of renal masses is the additional cost of undergoing a biopsy when surgery achieves both diagnosis and treatment objectives. However, if patients with benign tumors are spared the cost of treatment, biopsy may be cost effective. To address the cost effectiveness of RMB, Pandharipande and colleagues used a decisionanalytic Markhov model to compare cost effectiveness of using RMB to triage patient management to surveillance or empiric surgery for SRMs [Pandharipande et al. 2010]. They found that a biopsy strategy yielded a minimally improved quality-adjusted life expectancy of 4 days compared with surgery at a lower lifetime cost of $3466. In similar fashion, while again using a Markhov model, a more recent report compared immediate surgery with biopsy or surveillance in a hypothetical 60-year-old man with a SRM. When adjusting for quality of life, biopsy outperformed immediate surgery as a more cost-effective diagnostic strategy at $33,840 per quality-adjusted life year gained [Heilbrun et al. 2012]. Although biopsy did not yield the best survival, this study highlights that low-risk patients may be treated with surveillance for a T1a renal mass while benefiting from a cost-effective strategy. Ability of renal mass biopsy to diagnose the presence of malignancy The accuracy of RMB to diagnose malignancy depends on multiple factors, including the ability to target small tumors using imaging guidance, the ability to diagnose malignancy from small pathologic specimens, and the inherent sampling error when evaluating heterogeneous tumors. Although no prospective studies have evaluated fine needle aspiration (FNA) versus core biopsy techniques for accuracy, it should be noted that diagnoses from FNA sampling are considerably dependent on the experience of the cytopathologist, who may be present at the biopsy to confirm the adequacy of sampling [Volpe et al. 2007]. Nondiagnostic findings from RMB are present in 15–22% of large contemporary series [Shannon et al. 2008; Leveridge et al. 2011; Prince et al. 2014] (Table 2). Some of the variation in
incidence among series stems from the lack of a standardized definition for nondiagnostic RMB. Many series report only fibrosis or necrosis as nondiagnostic findings while other series include RMB with benign renal parenchyma when the tumor was ‘missed’. Nondiagnostic findings appear to be more common in patients with smaller tumors [Wang et al. 2009; Leveridge et al. 2011; Prince et al. 2014] and cystic features [Leveridge et al. 2011; Prince et al. 2014]. In addition, a longer distance from the skin to the tumor and a lack of enhancement with contrast imaging may also be associated with higher nondiagnostic rates [Prince et al. 2014]. Patient and tumor characteristics should be considered when deciding to obtain RMB, and lower overall nondiagnostic rates may be possible when selecting only patients with larger solid enhancing masses and shorter skin to tumor distance. When RMB is not diagnostic for either infection or a neoplasm, physicians should still suspect the presence of malignancy and consider repeating biopsy or proceeding with surgery or observation as indicated. However, there is minimal impact on risk stratification when physicians understand the continued risk of malignancy in patients with incidental renal masses and nondiagnostic RMB. Ability of renal mass biopsy to diagnose renal cell cancer subtypes Prior studies evaluating the concordance between biopsy specimens and surgical pathology for RCC subtype have ranged between 86% and 100% (Table 3) [Shannon et al. 2008; Wang et al. 2009; Millet et al. 2012]. High levels of concordance between biopsy and surgical pathology are especially noted in clear cell or conventional RCC [Shannon et al. 2008], which is the most common subtype of RCC [Lane et al. 2008]. Recent studies of non-clear cell RCC subtypes have also demonstrated high rates of concordance [Millet et al. 2012], with immunohistochemical staining facilitating diagnosis in some patients [Lane et al. 2008]. One important diagnostic consideration is the ability to differentiate between chromophobe RCC and oncocytoma, which may be achieved using a panel of tissue markers [Huang et al. 2009]. Historically, there was significant concern over the ability to distinguish oncocytoma from RCC both histologically and radiographically [Gakis et al. 2011] and surgical resection remained the only modality to diagnose and treat oncocytoma.
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Therapeutic Advances in Urology 7(5) Table 2. Renal mass biopsy series and nondiagnostic rate. Study
Biopsies
Nondiagnostic biopsy rate
Nondiagnostic definition
Maturen et al. [2007] Volpe et al. [2008] Prince et al. [2014] Leveridge et al. [2011] Lebret et al. [2007] Shannon et al. [2008] Vasudevan et al. [2006] Wang et al. [2009]
152 100
6 (3.9%) 16 (16%)
565
83 (14.7%)
345
67 (19.4%)
119
25 (21%)
235
51 (21.7%)
100 110
30 (30%) 10 (9%)
Insufficient tissue Insufficient tissue 1 RCC of 2 repeat biopsies Necrosis/fibrosis Insufficient tissue Nonrenal tissue Insufficient tissue 12 repeat biopsies revealed 8 RCCs Necrosis Inflammation 13 repeat biopsies revealed 11 RCCs Inflammation/necrosis Connective tissue Fat tissue Insufficient tissue 2 nondiagnostic biopsies were renal cell cancer after nephrectomy
Table 3. Studies comparing renal mass biopsy to surgical pathology. Study
Biopsy (n)
Subtype cancer diagnosis (%)
Grade concordance (%)
Grade concordance (%) (high or low)
Maturen et al. [2007] Volpe et al. [2008] Schmidbauer et al. [2008] Leveridge et al. [2011] Lebret et al. [2007] Blumenfeld et al. [2010] Millet et al. [2012]
59 100 60 100 52 67 61
98 66 96 88 86 82 100
70 68 76 64 46 43 75
Not shown 75 Not shown Not shown 74 64 93
Concern for hybrid tumors consisting of oncocytoma juxtaposed with malignant tissue [Waldert et al. 2010] caused many surgeons to recommend treatment for all patients despite a biopsy diagnosis of oncocytoma. However, recent series have suggested that hybrid tumors are exceptionally rare. Ginzburg and colleagues identified 147 solitary sporadic tumors that contained any element of oncocytoma or angiomyolipoma following nephrectomy [Ginzburg et al. 2014] and found less than 3% of tumors included coexistent malignant tissue, with no tumors having any high-grade components. Importantly, at a median follow up of 44 months, no patient with a hybrid tumor experienced local, regional or metastatic progression. These results are encouraging and support less aggressive approaches for renal oncocytoma management.
Ability of renal mass biopsy to evaluate tumor grade in renal cell carcinoma Tumor grade is often a reliable determinant of tumor behavior [Ficarra et al. 2010]. However, with recent studies demonstrating considerable tumor heterogeneity within RCC tumors, biopsy grade may be less accurate due to sampling error [Gerlinger et al. 2012]. To evaluate the possibility that tumor heterogeneity can lead to misrepresentation of biopsy grade, Ball and colleagues reevaluated 32 pT1a RCC surgical specimens for grade heterogeneity. Specimens consisted of either clear cell or papillary RCC with high- and low-grade features. The authors showed that 26 samples (81.3%) were heterogeneous and 15 of 16 high-grade tumors also exhibited significant low-grade components [Ball et al. 2015]. With significant grade heterogeneity demonstrated among high-grade
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ML Blute, Jr., A Drewry et al. cancers, it is obvious how biopsy sampling may miss a component of high-grade disease and underestimate RCC risk. Previous series substantiate the inaccuracy of predicting tumor grade from biopsy specimens [Neuzillet et al. 2004; Lebret et al. 2007; Millet et al. 2012], which has implications for reporting and interpreting RMB results. A recent report identified grade heterogeneity in single tumors in up to 25% of cases [Halverson et al. 2013]. Undergrading biopsy specimens could be significant clinically for some patients if they choose to defer treatment based on risk assessment from an erroneous tumor grade. The accuracy of tumor grading on RMB specimens varies considerably among series (43–75%) [Tomaszewski et al. 2014], and no studies included more than 100 patients. Although high-grade tumors are rare in small localized tumors [Abel et al. 2010b], the limited ability to predict tumor grade must be considered when making treatment decisions. Ability of preoperative imaging to evaluate tumor stage in small renal cell carcinoma Radiologic imaging may be used to evaluate the clinical T stage of the primary tumor, which is an important predictor of RCC recurrence and survival [Zisman et al. 2002; Sorbellini et al. 2005; Thompson et al. 2007], although clinical staging is not equivalent to pathologic staging in RCC. Renal masses equal to or less than 7 cm are staged as T1 or T3a when tumors invade into perinephric fat. However, imaging does not reliably identify perinephric fat invasion [Hedgire et al. 2013], which is an important predictor of poor outcomes in RCC. In a recent study of 860 patients with RCC stage T1–3 [Yoo et al. 2008], the authors showed a significant difference in disease-free survival [hazard ratio 2.21, 95% confidence interval (CI) 1.01–4.84; p = 0.05] among patients with fat invasion compared with lower stage disease. Furthermore, 85% of patients with recurrence of T3a tumors greater than 7 cm died of RCC compared with 33% of patients who had recurrence with tumors less than 7 cm (p = 0.001). When evaluating patients with tumors less than 7 cm specifically, metastatic recurrence was 14.6% compared with 6.0% in patients with fat invasion and without fat invasion, respectively [Ginzburg et al. 2014]. Siddiqui and colleagues also evaluated the significance of T3a disease across a spectrum of tumor size and found risk ratios of death for RCC fat invasion to be 6.15 (1.84–20.50, p = 0.003), 4.12 (2.50–6.78, p < 0.001) and 2.13 (1.53–2.97, p < 0.001) for tumors 4 cm or smaller, 4–7 cm, and more than 7
cm, respectively [Siddiqui et al. 2007]. The association of death with fat invasion remained significant on multivariate analysis. Attempts to identify T3a tumors based on preoperative imaging have demonstrated poor accuracy [Sokhi et al. 2015]. A recent study compared a combined approach of computed tomography/magnetic resonance imaging with nephrectomy assessment for perinephric fat invasion in renal masses with median diameter of 4.5 cm. Of 55 patients who were diagnosed with fat invasion, 26 (47.2%) did not have pathological fat invasion [Huang et al. 2009]. Likewise, detection of renal sinus fat invasion may carry equal importance as these tumors have been shown to be more aggressive than tumors with perinephric fat involvement [Thompson et al. 2005]. Unless more reliable methods for detecting perinephric fat and renal sinus fat invasion [Kim et al. 2014] are developed, understaging will likely remain a persistent limitation for approximately 5–10% of patients with clinically localized tumors that are pathologically T3a [Siddiqui et al. 2007; Gorin et al. 2013]. Ability of biopsy to identify aggressive pathologic features in small renal masses Sarcomatoid dedifferentiation is an aggressive pathologic feature that may be present with any RCC subtype [Lane et al. 2008] and is associated with poor outcomes [Zhang et al. 2014]. However, the ability of percutaneous biopsy to identify sarcomatoid features may be limited by sampling error. In patients with mRCC, sarcomatoid dedifferentiation was identified preoperatively in only 11.8% and 9.2% of primary tumors and metastatic tumors, respectively [Chao et al. 2001; Crispen et al. 2011]. As seen with high tumor grade [Ball et al. 2015], sarcomatoid dedifferentiation may only be present in a minority of tissue and percutaneous biopsy is therefore prone to sampling error. However, sarcomatoid pathology is rare in lower stage tumors, with one study of 925 patients with pT1 and pT2 tumors demonstrating less than 1% incidence of sarcomatoid features in the surgical specimens [Abel et al. 2010b]. Given the rarity in low-stage tumors, the inability to identify sarcomatoid features from biopsy is likely less significant for this population. Should the limitations of biopsy limit its use for risk stratification of incidental renal masses? There are notable limitations (Table 4) when using RMB that may result in underestimation of risk in patients with nonmetastatic disease and incidental renal masses. These limitations should
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Therapeutic Advances in Urology 7(5) Table 4. Potential limitations when using renal mass biopsy for estimating risk from incidental renal masses. Nondiagnostic findings in approximately 15% of patients Underestimation of grade in approximately 25% of patients Underestimation of stage in approximately 5–10% of patients Failure to identify aggressive pathology, that is sarcomatoid or rhabdoid features
be considered when ordering RMB for healthy patients considering surgical treatment, because of the risk of mRCC. However, the potential benefits of RMB for many patients should not be dismissed regardless of RMB limitations. Biopsy is safe and likely cost efficient when used judiciously and has demonstrated the ability to reliably identify malignant and benign tumors in patients with incidental renal masses. For many patients with incidental renal masses, RMB can provide information that is helpful for management. Patient selection for renal mass biopsy Selecting appropriate patients for RMB is important to improve the evaluation of incidental renal masses and maximize the percentage of patients who benefit from this procedure. Patients who are considering active surveillance or thermal ablation should receive RMB in order to plan appropriate follow-up protocols [Volpe et al. 2012]. When benign masses are identified, patients may receive minimal follow up as appropriate. Similarly, in patients who are borderline candidates for surgery, the identification of benign masses allows surgery to be deferred. However, in patients with comorbidities that significantly limit a patient’s life expectancy, RMB should only be ordered when the information gained from RMB may change the patient’s further treatment. Patients with atypical renal masses that are concerning for infection or metastatic lesions are ideal patients for RMB. In addition, very young patients or those with masses that are suspicious for nonRCC lesions may benefit from identification of malignancy, as treatment for some tumors such as renal lymphomas [Cyriac et al. 2010] or sarcomas [De Visschere et al. 2013] may involve upfront chemotherapy or radiation therapy. Deciding which patients should receive RMB among patients who are otherwise acceptable surgical candidates is less clear. However, RMB does improve informed consent for patients who are considering surgical treatment for their renal masses. When patients are given the diagnosis of cancer from RMB, they may be more willing to be treated with surgical therapy.
Conversely, patients with benign masses identified from RMB may be more willing to undergo observation. Patients who are suspected of having metastatic renal masses may also obtain RMB for diagnosis, especially as the majority of patients with mRCC are not treated with cytoreductive nephrectomy [Tsao et al. 2012; Minnillo et al. 2014], but need a pathologic diagnosis prior to treatment. Despite the development of multiple new therapies, patients with mRCC continue to have a poor prognosis [Heng et al. 2009]. Aggressive features such as sarcomatoid dedifferentiation are associated with short overall survival and may not benefit from cytoreductive surgery [Mian et al. 2002; Molina et al. 2011; Przybycin et al. 2014]. An analysis of 417 patients undergoing cytoreductive nephrectomy for mRCC compared those with sarcomatoid histology with conventional RCC [Shuch et al. 2009]. Median survival in patients with sarcomatoid features was just 4.9 months compared with 17.7 months for conventional clear cell RCC (p < 0.001). However, sarcomatoid features are difficult to identify because of sampling error in large tumors or metastases using standard biopsy techniques [Abel et al. 2010a, 2012]. Similarly, distinguishing non-clear cell tumor subtypes may be helpful as targeted therapy appear to be less effective [Vera-Badillo et al. 2014]. In a meta-analysis consisting of 49 studies and 7771 patients treated with targeted therapy for mRCC, the median progression-free survival and overall survival for nonclear cell RCC was 7.4 and 13.4 months, respectively, compared with 10.5 and 15.7 months for clear cell RCC, respectively (p < 0.001). While cytoreductive nephrectomy may provide a survival benefit in metastatic non-clear cell RCC [Aizer et al. 2014], preoperative identification of non-clear cell RCC from RMB may allow enrollment in clinical trials of presurgical therapy. Clinical protocols for decision making using renal mass biopsy for incidental renal masses Information gained from biopsy may allow improved patient selection for surgery and other
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ML Blute, Jr., A Drewry et al. treatments. Several studies have critically analyzed the ability of RMB to impact decision making, although the optimal use remains debated. Halverson and colleagues evaluated 133 patients with SRMs and assigned patients to surgery or surveillance based on RMB findings [Halverson et al. 2013]. Of the 97 tumors that were assigned to surgery, agreement between biopsy and final pathology was 100% for identifying malignancy and 94% for distinguishing histology. According to their model, biopsy correctly assigned all 97 patients (90% sensitivity) to surgery while 11 of 36 patients were incorrectly assigned to surveillance based on final pathology. For the entire cohort, agreement between biopsy and final pathology was 92% (95% CI 0.64–0.90). Similarly, Tan et al. analyzed the role of RMB for SRMs to guide decision making [Tan et al. 2012]. The authors determined indications for RMB in 78 (38%) of 204 patients with T1 tumors and identified body mass index greater than 25, juxtahilar tumor location, and high R.E.N.A.L. (it is an acronym for Radius, Exophytic/endophytic properties, Nearness of tumor to hilum, Anterio/posterior, Location) nephrometry score as factors associated with use of RMB on multivariate analysis. The authors conclude that RMB was able to direct treatmentrelated decision making, with surveillance planned more often for patients with favorable and benign histology and surgical management reserved for aggressive tumors (p < 0.001). The approaches in these two studies highlight the potential for RMB to improve clinical decision making as more asymptomatic renal tumors are diagnosed by cross-sectional imaging. However, the limitations of RMB (Table 4) should be discussed with patients who are risk stratified using these approaches, given the risks with this approach. Biopsy for evaluation of incidental renal masses: potential impact on patient care Approximately 20–30% of renal masses are benign following surgical resection [Frank et al. 2003; Gill et al. 2003]. If RMB could reliably identify these patients prior to surgery, a significant proportion of patients with benign tumors could be spared surgery. Despite noted RMB limitations (Table 4), the majority of series have demonstrated accuracy to distinguish between benign and malignant tumors, when biopsy findings are diagnostic. Avoiding treatment in patients with benign tumors would improve overall renal function, as fewer patients would have treatmentrelated loss of renal function. In addition, patients
with benign tumors could be spared the risk of treatment-related complications and the cost of treatment. Another potential impact of routine RMB that is difficult to measure empirically is the improved ability for informed consent after RMB in patients considering definitive management. Patient awareness of biopsy-proven malignancy may lead to a more informed and assertive decision for management, which appears reasonable given the low procedural morbidity. When atypical renal masses are diagnosed from imaging [Leveridge et al. 2010], RMB also allows for distinguishing between rare tumors and uncommon presentations of common tumors, which may also impact management for tumors when nonsurgical treatment is indicated. Conclusion Risk stratifying patients with unknown renal masses is important when choosing an acceptable treatment. RMB is associated with a low incidence of complications and may provide valuable information to help patients and physicians decide among treatments. It is important to recognize that RMB may underestimate risk and has limited accuracy when evaluating tumor grade, aggressive pathologic features or T stage. Future studies are necessary to evaluate the optimal use of biopsy in the evaluation and management of incidental renal masses. Funding No outside funding was used in this project. Conflict of interest statement The authors declare that there is no conflict of interest.
References Abel, E., Carrasco, A., Culp, S., Matin, S., Tamboli, P., Tannir, N. et al. (2012) Limitations of preoperative biopsy in patients with metastatic renal cell carcinoma: comparison to surgical pathology in 405 cases. BJU Int 110: 1742–1746. Abel, E., Culp, S., Matin, S., Tamboli, P., Wallace, M., Jonasch, E. et al. (2010a) Percutaneous biopsy of primary tumor in metastatic renal cell carcinoma to predict high risk pathological features: comparison with nephrectomy assessment. J Urol 184: 1877–1881. Abel, E., Culp, S., Meissner, M., Matin, S., Tamboli, P. and Wood, C. (2010b) Identifying the risk of
http://tau.sagepub.com 271
Therapeutic Advances in Urology 7(5) disease progression after surgery for localized renal cell carcinoma. BJU Int 106: 1277–1283. Aizer, A., Urun, Y., McKay, R., Kibel, A., Nguyen, P. and Choueiri, T. (2014) Cytoreductive nephrectomy in patients with metastatic non-clear-cell renal cell carcinoma (RCC). BJU Int 113: E67–E74. Ball, M., Bezerra, S., Gorin, M., Cowan, M., Pavlovich, C., Pierorazio, P. et al. (2015) Grade heterogeneity in small renal masses: potential implications for renal mass biopsy. J Urol 193: 36–40. Blumenfeld, A.J., Guru, K., Fuchs, G.J. and Kim, H.L. (2010) Percutaneous biopsy of renal cell carcinoma underestimates nuclear grade. Urology 76(3): 610–603. Caoili, E., Bude, R., Higgins, E., Hoff, D. and Nghiem, H. (2002) Evaluation of sonographically guided percutaneous core biopsy of renal masses. AJR Am J Roentgenol 179: 373–378. Chao, D., Zisman, A., Freedland, S., Pantuck, A., Said, J. and Belldegrun, A. (2001) Sarcomatoid renal cell carcinoma: basic biology, clinical behavior and response to therapy. Urol Oncol 6: 231–238. Choueiri, T., Schutz, F., Hevelone, N., Nguyen, P., Lipsitz, S., Williams, S. et al. (2011) Thermal ablation vs surgery for localized kidney cancer: a Surveillance, Epidemiology, and End Results (SEER) database analysis. Urology 78: 93–98. Crispen, P., Breau, R., Allmer, C., Lohse, C., Cheville, J., Leibovich, B. et al. (2011) Lymph node dissection at the time of radical nephrectomy for highrisk clear cell renal cell carcinoma: indications and recommendations for surgical templates. Eur Urol 59: 18–23. Cyriac, S., Rejiv, R., Shirley, S. and Sagar, G. (2010) Primary renal lymphoma mimicking renal cell carcinoma. Indian J Urol 26: 441–443. De Visschere, P., De Potter, A., Claus, F., Mulkens, T., Oyen, R., Verbaeys, A. et al. (2013) PNET/ Ewing’s sarcoma of the kidney: imaging findings in two cases. JBR-BTR 96: 75–77. Ficarra, V., Brunelli, M., Cheng, L., Kirkali, Z., Lopez-Beltran, A., Martignoni, G. et al. (2010) Prognostic and therapeutic impact of the histopathologic definition of parenchymal epithelial renal tumors. Eur Urol 58: 655–668.
Gerlinger, M., Rowan, A., Horswell, S., Larkin, J., Endesfelder, D., Gronroos, E. et al. (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366: 883–892. Gill, I., Matin, S., Desai, M., Kaouk, J., Steinberg, A., Mascha, E. et al. (2003) Comparative analysis of laparoscopic versus open partial nephrectomy for renal tumors in 200 patients. J Urol 170: 64–68. Ginzburg, S., Uzzo, R., Al-Saleem, T., Dulaimi, E., Walton, J., Corcoran, A. et al. (2014) Coexisting hybrid malignancy in a solitary sporadic solid benign renal mass: implications for treating patients following renal biopsy. J Urol 191: 296–300. Gorin, M., Ball, M., Pierorazio, P., Tanagho, Y., Bhayani, S., Kaouk, J. et al. (2013) Outcomes and predictors of clinical T1 to pathological T3a tumor up-staging after robotic partial nephrectomy: a multiinstitutional analysis. J Urol 190: 1907–1911. Halverson, S., Kunju, L., Bhalla, R., Gadzinski, A., Alderman, M., Miller, D. et al. (2013) Accuracy of determining small renal mass management with risk stratified biopsies: confirmation by final pathology. J Urol 189: 441–446. Hedgire, S., Elmi, A., Nadkarni, N., Cao, K., McDermott, S. and Harisinghani, M. (2013) Preoperative evaluation of perinephric fat invasion in patients with renal cell carcinoma: correlation with pathological findings. Clin Imaging 37: 91–96. Heilbrun, M., Yu, J., Smith, K., Dechet, C., Zagoria, R. and Roberts, M. (2012) The cost-effectiveness of immediate treatment, percutaneous biopsy and active surveillance for the diagnosis of the small solid renal mass: evidence from a Markov model. J Urol 187: 39–43. Heng, D., Xie, W., Regan, M., Warren, M., Golshayan, A., Sahi, C. et al. (2009) Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 27: 5794–5799. Hollingsworth, J., Miller, D., Daignault, S. and Hollenbeck, B. (2006) Rising incidence of small renal masses: a need to reassess treatment effect. J Natl Cancer Inst 98: 1331–1334.
Frank, I., Blute, M., Cheville, J., Lohse, C., Weaver, A. and Zincke, H. (2003) Solid renal tumors: an analysis of pathological features related to tumor size. J Urol 170: 2217–2220.
Huang, W., Kanehira, K., Drew, S. and Pier, T. (2009) Oncocytoma can be differentiated from its renal cell carcinoma mimics by a panel of markers an automated tissue microarray study. Appl Immunohistochem Mol Morphol 17: 12–17.
Gakis, G., Kramer, U., Schilling, D., Kruck, S., Stenzl, A. and Schlemmer, H. (2011) Small renal oncocytomas: differentiation with multiphase CT. Eur J Radiol 80: 274–278.
Kim, C., Choi, H. and Cho, K. (2014) Diagnostic value of multidetector computed tomography for renal sinus fat invasion in renal cell carcinoma patients. Eur J Radiol 83: 914–918.
272 http://tau.sagepub.com
ML Blute, Jr., A Drewry et al. Kutikov, A., Egleston, B., Wong, Y. and Uzzo, R. (2010) Evaluating overall survival and competing risks of death in patients with localized renal cell carcinoma using a comprehensive nomogram. J Clin Oncol 28: 311–317. Lane, B., Samplaski, M., Herts, B., Zhou, M., Novick, A. and Campbell, S. (2008) Renal mass biopsy–a renaissance? J Urol 179: 20–27. Lebret, T., Poulain, J., Molinie, V., Herve, J., Denoux, Y., Guth, A. et al. (2007) Percutaneous core biopsy for renal masses: indications, accuracy and results. J Urol 178: 1184–1188; discussion 1188. Leppert, J., Hanley, J., Wagner, T., Chung, B., Srinivas, S., Chertow, G. et al. (2014) Utilization of renal mass biopsy in patients with renal cell carcinoma. Urology 83: 774–779. Leveridge, M., Bostrom, P., Koulouris, G., Finelli, A. and Lawrentschuk, N. (2010) Imaging renal cell carcinoma with ultrasonography, CT and MRI. Nat Rev Urol 7: 311–325. Leveridge, M., Finelli, A., Kachura, J., Evans, A., Chung, H., Shiff, D. et al. (2011) Outcomes of small renal mass needle core biopsy, nondiagnostic percutaneous biopsy, and the role of repeat biopsy. Eur Urol 60: 578–584. Maturen, K.E., Nghiem, H.V., Caoili, E.M., Higgins, E.G., Wolf, J.S. Jr. and Wood, D.P. Jr. (2007) Renal mass core biopsy: accuracy and impact on clinical management. AJR Am J Roentgenol 188(2): 563–570. Mian, B., Bhadkamkar, N., Slaton, J., Pisters, P., Daliani, D., Swanson, D. et al. (2002) Prognostic factors and survival of patients with sarcomatoid renal cell carcinoma. J Urol 167: 65–70. Millet, I., Curros, F., Serre, I., Taourel, P. and Thuret, R. (2012) Can renal biopsy accurately predict histological subtype and Fuhrman grade of renal cell carcinoma? J Urol 188: 1690–1694. Minnillo, B., Zhu, H., Maurice, M. and Abouassaly, R. (2014) Trends in cytoreductive nephrectomy in the eras of immuno and targeted therapy. J Clin Oncol 32(Suppl. 4): abstract 472. Molina, A., Tickoo, S., Ishill, N., Trinos, M., Schwartz, L., Patil, S. et al. (2011) Sarcomatoidvariant renal cell carcinoma: treatment outcome and survival in advanced disease. Am J Clin Oncol 34: 454–459. Mullins, J. and Rodriguez, R. (2013) Renal cell carcinoma seeding of a percutaneous biopsy tract. Can Urol Assoc J 7: E176–E179. Neuzillet, Y., Lechevallier, E., Andre, M., Daniel, L. and Coulange, C. (2004) Accuracy and clinical role of fine needle percutaneous biopsy with computerized
tomography guidance of small (less than 4.0 cm) renal masses. J Urol 171: 1802–1805. Nguyen, M., Gill, I. and Ellison, L. (2006) The evolving presentation of renal carcinoma in the United States: trends from the surveillance, epidemiology, and end results program. J Urol 176: 2397–2400. Pandharipande, P., Gervais, D., Hartman, R., Harisinghani, M., Feldman, A., Mueller, P. et al. (2010) Renal mass biopsy to guide treatment decisions for small incidental renal tumors: a costeffectiveness analysis. Radiology 256: 836–846. Pantuck, A., Zisman, A. and Belldegrun, A. (2001) The changing natural history of renal cell carcinoma. J Urol 166: 1611–1623. Patel, N., Cranston, D., Akhtar, M., George, C., Jones, A., Leiblich, A. et al. (2012) Active surveillance of small renal masses offers short-term oncological efficacy equivalent to radical and partial nephrectomy. BJU Int 110: 1270–1275. Prince, J., Bultman, E., Hinshaw, L., Drewry, A., Blute, M., Best, S. et al. (2014) Patient and tumor characteristics can predict non-diagnostic renal mass biopsy findings. J Urol 5347: 05062–05069. Przybycin, C., McKenney, J., Reynolds, J., Campbell, S., Zhou, M., Karafa, M. et al. (2014) Rhabdoid differentiation is associated with aggressive behavior in renal cell carcinoma: a clinicopathologic analysis of 76 cases with clinical follow-up. Am J Surg Pathol 38: 1260–1265. Rybicki, F., Shu, K., Cibas, E., Fielding, J., van Sonnenberg, E. and Silverman, S. (2003) Percutaneous biopsy of renal masses: sensitivity and negative predictive value stratified by clinical setting and size of masses. AJR Am J Roentgenol 180: 1281–1287. Schmidbauer, J., Remzi, M., Memarsadeghi, M., Haitel A., Klingler, H.C., Katzenbeisser, D. et al. (2008) Diagnostic accuracy of computed tomographyguided percutaneous biopsy of renal masses. Eur Urol 53(5): 1003–1011. Shannon, B., Cohen, R., de Bruto, H. and Davies, R. (2008) The value of preoperative needle core biopsy for diagnosing benign lesions among small, incidentally detected renal masses. J Urol 180: 1257–1261; discussion 1261. Shuch, B., Said, J., La Rochelle, J., Zhou, Y., Li, G., Klatte, T. et al. (2009) Cytoreductive nephrectomy for kidney cancer with sarcomatoid histology – is up-front resection indicated and, if not, is it avoidable? J Urol 182: 2164–2171. Siddiqui, S., Frank, I., Leibovich, B., Cheville, J., Lohse, C., Zincke, H. et al. (2007) Impact of tumor size on the predictive ability of the pT3a primary tumor classification for renal cell carcinoma. J Urol 177: 59–62.
http://tau.sagepub.com 273
Therapeutic Advances in Urology 7(5) Smaldone, M., Corcoran, A. and Uzzo, R. (2013) Active surveillance of small renal masses. Nat Rev Urol 10: 266–274. Sokhi, H, Mok, W. and Patel, U. (2015) Stage T3a renal cell carcinoma: staging accuracy of CT for sinus fat, perinephric fat or renal vein invasion. Br J Radiol 88: 20140504. Sorbellini, M., Kattan, M., Snyder, M., Reuter, V., Motzer, R., Goetzl, M. et al. (2005) A postoperative prognostic nomogram predicting recurrence for patients with conventional clear cell renal cell carcinoma. J Urol 173: 48–51. Tan, H., Jacobs, B., Hafez, K., Montgomery, J., Weizer, A., Wood, D. et al. (2012) Understanding the role of percutaneous biopsy in the management of patients with a small renal mass. Urology 79: 372–377. Thompson, R., Leibovich, B., Cheville, J., Webster, W., Lohse, C., Kwon, E. et al. (2005) Is renal sinus fat invasion the same as perinephric fat invasion for pT3a renal cell carcinoma? J Urol 174: 1218–1221. Thompson, R., Leibovich, B., Lohse, C., Cheville, J., Zincke, H., Blute, M. et al. (2007) Dynamic outcome prediction in patients with clear cell renal cell carcinoma treated with radical nephrectomy: the D-SSIGN score. J Urol 177: 477–480.
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Vera-Badillo, F., Templeton, A., Duran, I., Ocana, A., de Gouveia, P., Aneja, P. et al. (2014) Systemic therapy for non-clear cell renal cell carcinomas: a systematic review and meta-analysis. Eur Urol 67: 740–749. Volpe, A., Finelli, A., Gill, I., Jewett, M., Martignoni, G., Polascik, T. et al. (2012) Rationale for percutaneous biopsy and histologic characterisation of renal tumours. Eur Urol 62: 491–504. Volpe, A., Kachura, J., Geddie, W., Evans, A., Gharajeh, A., Saravanan, A. et al. (2007) Techniques, safety and accuracy of sampling of renal tumors by fine needle aspiration and core biopsy. J Urol 178: 379–386. Volpe, A., Mattar, K., Finelli, A., Kachura, J.R., Evans, A.J., Geddie, W.R. et al. (2008) Contemporary results of percutaneous biopsy of 100 small renal masses: a single center experience. J Urol 180(6): 2333–2337. Waldert, M., Klatte, T., Haitel, A., Ozsoy, M., Schmidbauer, J., Marberger, M. et al. (2010) Hybrid renal cell carcinomas containing histopathologic features of chromophobe renal cell carcinomas and oncocytomas have excellent oncologic outcomes. Eur Urol 57: 661–665.
Tomaszewski, J., Uzzo, R. and Smaldone, M. (2014) Heterogeneity and renal mass biopsy: a review of its role and reliability. Cancer Biol Med 11: 162–172.
Wang, R., Wolf, J., Wood, D., Higgins, E. and Hafez, K. (2009) Accuracy of percutaneous core biopsy in management of small renal masses. Urology 73: 586–590; discussion 590–591.
Tsao, C., Small, A., Moshier, E., Gartrell, B., Wisnivesky, J., Sonpavde, G. et al. (2012) Trends in the use of cytoreductive nephrectomy in the United States. Clin Genitourin Cancer 10: 159–163.
Yoo, C., Song, C., Hong, J., Kim, C. and Ahn, H. (2008) Prognostic significance of perinephric fat infiltration and tumor size in renal cell carcinoma. J Urol 180: 486–491; discussion 491.
Umbreit, E., Shimko, M., Childs, M., Lohse, C., Cheville, J., Leibovich, B. et al. (2012) Metastatic potential of a renal mass according to original tumour size at presentation. BJU Int 109: 190–194; discussion 194.
Zhang, B., Thompson, R., Lohse, C., Leibovich, B., Boorjian, S., Cheville, J. et al. (2014) A novel prognostic model for patients with sarcomatoid renal cell carcinoma. BJU Int 115: 405–411.
Vasudevan, A., Davies, R.J., Shannon, B.A. and Cohen, R.J. (2006) Incidental renal tumours: the frequency of benign lesions and the role of preoperative core biopsy. BJU Int 97(5): 946–949.
Zisman, A., Pantuck, A., Wieder, J., Chao, D., Dorey, F., Said, J. et al. (2002) Risk group assessment and clinical outcome algorithm to predict the natural history of patients with surgically resected renal cell carcinoma. J Clin Oncol 20: 4559–4566.
274 http://tau.sagepub.com
